Cardiopulmonary arrest (CA) is a major cause of death and disability in the US. CA affects up to 325,000 people each year with only a 10% survival rate. The whole-body ischemia following CA results in subsequent brain damage resulting in neurological deficits. Our long-term goal is to decrease brain damage by reviving cerebral blood flow and subsequent neurological deficits associated with CA. Therefore, it is important to understand the mechanism(s) underlying CA-induced brain injury. The importance of identifying regulatory factors that influence cerebral blood flow autoregulation and innovative neuroprotective agents in the context of CA is paramount to change the outcomes following CA and it is the main goal of this proposal. We propose to study a new vasotone regulatory mechanism, the release of palmitic acid methyl ester (a vasodilator and neuroprotectant) derived from the superior cervical ganglion innervating major cerebral arteries. Our central hypothesis is that protein arginine methyltransferases are the regulatory ?switch? for the methylation of palmitic acid to form palmitic acid methyl ester responsible for vasodilation/neuroprotection during ischemia.
Survival rates following cardiac arrest are poor, despite prompt emergency treatment and better resuscitation techniques with 70,000 patients per year that are resuscitated after cardiac arrest, 60% die from extensive brain injury and only 3?10% are able to resume their former lifestyles. Most neuroprotective trials for cerebral ischemia have been unsuccessful and therefore, new interventions are greatly needed. Our goal in this proposal is to understand sympathetic regulation in brain circulation after cardiac arrest, in order to lay the foundation for a common therapy and greatly improve the outcome from cardiac arrest.
|Lee, Reggie H C; Lee, Michelle H H; Wu, Celeste Y C et al. (2018) Cerebral ischemia and neuroregeneration. Neural Regen Res 13:373-385|
|Wu, Celeste Y C; Lerner, Francesca M; Couto E Silva, Alexandre et al. (2018) Utilizing the Modified T-Maze to Assess Functional Memory Outcomes After Cardiac Arrest. J Vis Exp :|